Fifteen years after 9/11, many World Trade Center (WTC) responders continue to suffer from signature WTC- related physical and mental disorders. Prevalent and persistent comorbidity between these disorders challenges traditional treatments. The present proposal aims to explicate vulnerability and resilience factors in WTC responders, and use this knowledge to develop a person-focused care model for comorbid medical and psychiatric conditions. The proposal focuses on personality, which in preliminary cross-sectional studies of WTC responder population was among the strongest predictors of physical and mental disorders, persistence of symptoms, social and occupational impairment, and treatment utilization, even when controlling for WTC- related diagnoses. This is in line with the literature confirming that personality is one of the most powerful predictors of vulnerability and resilience in response to disasters, leading to large differences in illness course and treatment response, which person-focused medicine can recognize and address. However, longitudinal investigation is necessary to establish that personality predicts outcomes and elucidate specific mechanisms by which it affects illness course. Furthermore, the feasibility of personality-informed care model that targets personality vulnerability in addition to physical and mental disorders remains to be evaluated. The current study will recruit and follow 400 WTC responders from Long Island site of the WTC Health Program as they present for annual monitoring. In the observational part of the study, participants will complete a state-of-the-art personality assessment during the baseline visit. At that and at two subsequent annual visits, they will complete, during 1 week, daily measures of symptoms, lung function, cognitive processes, stressors, and functional impairment, and we will also obtain their diagnostic and services information. These analyses will determine which personality vulnerabilities uniquely contribute to worse illness course, functioning and treatment utilization, and clarify the underpinning mechanisms. Furthermore, this information will allow a construction of a predictive model and will identify key vulnerabilities that can be targets of treatment. The treatment part of the study will test the feasibility of improving health outcomes by treating personality vulnerabilities using an approach informed by the constructed model. We will target the most significant of these vulnerabilities in a proof-of-concept randomized clinical trial (RCT), where 60 patients with comorbid disorders who have the vulnerability will be randomized to personality-informed treatment (PT) vs. control treatment (CT). We hypothesize that PT will be more effective in changing this vulnerability and related mechanisms than CT. Taken together, the proposed study will be the first to rigorously investigate personality assessment as a tool of personality-informed medicine to predict and treat mental and physical comorbidity in WTC responders. This will inform the healthcare provision for WTC responders and will also be relevant to other health care systems.